Water → 3-chloro-N-(3,4-difluorophenyl)propanamide

HRID 344877Notes

Reaction equation

HRID 344877 reaction equation
[Cl:1][CH2:2][CH2:3][C:4](Cl)=[O:5].[F:7][C:8]1[CH:9]=[C:10]([CH:12]=[CH:13][C:14]=1[F:15])[NH2:11].O>N1C=CC=CC=1.CC(C)=O.CCCCCC>[F:7][C:8]1[CH:9]=[C:10]([CH:12]=[CH:13][C:14]=1[F:15])[NH:11][C:4](=[O:5])[CH2:3][CH2:2][Cl:1]

Participants

7

Reactant 3

HCID 962WaterHCID 693643-Chloropropionyl chlorideHCID 774693,4-Difluoroaniline

Product 1

HCID 34714033-chloro-N-(3,4-difluorophenyl)propanamideYield 95.4%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 1049PyridineSolventHCID 8058HexaneSolvent

Conditions

Temperature
20 °C

Procedure

3-Chloropropionyl chloride (139.16 g) is added with stirring in the course of 1 hour and a half to a solution, heated to a temperature in the region of 55° C., of 3,4-difluoroaniline (125 g) in pyridine (80 cc) and acetone (1.5 liters), and the mixture is maintained at this temperature for 1 hour and a half. After cooling to approximately 20° C., the solution is poured with stirring into a mixture of water (1 liter) and crushed ice (500 g). The temperature is allowed to rise to approximately 20° C. and the product is extracted with dichloromethane (3×500 cc). The combined organic extracts are washed with N hydrochloric acid (500 cc) and water (5×500 cc), dried over magnesium sulphate, filtered and concentrated under reduced pressure (20 kPa) at approximately 50° C. The solid obtained is taken up in n-hexane (500 cc), drained and washed with the same solvent (2×100 cc). 3',4'-Difluoro-3-chloropropionanilide (202.9 g) is obtained in the form of a beige solid, m.p. 76° C., which is used without further purification for the subsequent steps.

Workup

  1. temperaturethe mixture is maintained at this temperature for 1 hour
  2. additionthe solution is poured
  3. customto rise to approximately 20° C.
  4. extractionthe product is extracted with dichloromethane (3×500 cc)
  5. washThe combined organic extracts are washed with N hydrochloric acid (500 cc) and water (5×500 cc)
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure (20 kPa) at approximately 50° C
  9. customThe solid obtained
  10. washwashed with the same solvent (2×100 cc)

Sources & evidence

ORD record
ord-10e65b65d28f4eb1b49ab675f44dc575
Source dataset
uspto-grants-1991_10
Patent number
US05053509

Reaction notes

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